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Tuesday, May 5, 2015

Germline DNA changes and bioethics

The BBC reports that Francis Collins, Director of the NIH, will not allow that agency to sponsor research on germline gene transfer. Various new technologies seem promising in terms of being able to select a specific part of the genome that contains a clearly defective sequence, and replace that with a normal or healthy sequence. Much of biotechnology is actually borrowed from what bacteria do naturally, as is the case for a recent approach, called CRISPR.

Genetic engineering has long been seen as the obvious thing to do when a clearly defective gene or genome segment is identified. We are among the most skeptical when it comes to claims about high predictive power of genotypes relative to many human conditions, but there are clearly hundreds of known genetic variants that seem to have high 'penetrance', that is, are likely to cause disease or a disorder when present, and thus have high predictive power for serious, often pediatric diseases. These disorders can devastate the person's entire life, so that prevention would be better than therapy once they've occurred. The idea of germline genetic engineering is to prevent the problem--and, indeed, do so permanently even in that individual's descendants. It is the direct way to treat a defective gene by preventing its consequences in the first place, while other therapeutic approaches only work on the defect once it has been inherited.

Dr Collins notes that these current methods are by no means yet foolproof. Germline engineering also seems to cross an ethical or even religious line in terms of meddling with Mother Nature. In the BBC story, he notes that embryo screening already can identify those embryos not carrying the harmful genetic material, those that are healthy to begin with (with respect to tested variants, at least), and can then be used without the risk of trying to engineer a change artificially, where mistakes can arise. The problems with the CRISPR method at present include unwanted or undocumented changes elsewhere in the genome, and these could have serious consequences for the individual (and, again, his/her future offspring).

This seems to be a somewhat ironic, but sound, decision at least for the moment. The idea of preventing harmful genetic conditions by removing them from our human patrimony is a noble one and has been seen as just around the corner ever since the modern era of molecular genetic technologies. But genomes are complex, and one tinkers at one's peril, based on what is currently known.

Selective embryo choice has its own ethical issues, of course, as does abortion, cloning, or any tinkering with our nature. Ethics are not always shared, however, and people vary in their ideas of right and wrong. Indeed, ethical restraints don't always fare well in competition with selfish interests, which is why institutions and governments impose ethical considerations on research. Even if the NIH prevents germline genetic engineering, we probably cannot stop other countries and private companies from doing it. Profits are to be made and, to be fair, parents' dreams of normal children will be catered to, hopefully in a positive way. Generally, it is hard to believe that self-interests will not over-ride ethical interests, as they so often do when money is to be made. Which is not to say that profit is the only motive--there is good to be done, and lives to improve as well.

Of course, germline engineering of various sorts is taking place in plants and animals for agricultural purposes. The original level of controversy in terms of feasibility has seemingly waned and cloned animals and plants are routinely being made. GMO plants are still controversial for many reasons both including potential health issues and, perhaps even more so, the economics of industrialized, highly profitable agriculture, especially as it impacts the developing world and distracts attention from more sustainable, soil-preserving practices. At present it is hard to sort out the issues there, given the strength and diversity of feelings, and the hard-core economic and vested-interest issues involved. But it is always risky to bet against the power of technology to solve problems, and even to do that in an ethical way.

There are many who advocate genetic engineering for entirely good, moral reasons, related to human improvement. But there are many also who are not willing to wait until things are shown to be safe. In any case, at present, Dr Collins seems to be doing what he can to keep the Dr Frankensteins under control. Whether it's a losing battle, and whether indeed far more good than evil will come from human germline manipulation, remain to be seen. One can hope that the best will triumph.

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